Vesicle Transporter USO1 Regulates Triple Negative Breast Cancer Cell Growth through mTOR/4EBP1 Pathway
PEI Yanqing1*, CHEN Xiaonan2
To explore the role and mechanism of USO1 in TNBC (triple negative breast cancer), this study first compared the expression level of USO1 in different breast cancer cells, and selected MDA-MB-231 and MDA-MB-453 cells to construct USO1 knockdown and overexpression cell lines. The mRNA expression level of USO1 was detected by RT-PCR, protein expression level was detected by Western blot, cell proliferation activity was detected by CCK-8, colony formation ability was detected by colony assay, cell cycle was detected by flow cytometry, and tumor growth was detected by tumor bearing assay in nude mice. The results showed that USO1 expression was elevated in breast cancer tissues, which was closely associated with poor prognosis of the patients, and the expression level of USO1 in TNBC cells was higher than that in non-TNBC cells. Knockdown of USO1 resulted in G1/S cell cycle arrest and inhibited TNBC cell proliferation, colony formation and tumor-bearing growth. Knockdown or overexpression of USO1 inhibits or promotes the expression of p-mTOR, p4EBP1, Cyclin D and Cyclin E. In conclusion, USO1 accelerates the G1/S phase transformation of TNBC cell cycle by activating the mTOR/4EBP1 signaling pathway, thus promoting tumor growth, and it is a potential therapeutic target of TNBC.
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